SCA2 in the Indian population: Unified haplotype and variable phenotypic patterns in a large case series.

BACKGROUND: Spinocerebellar ataxia-2 is one of the most prevalent SCA type across the world and one of the commonest in India. We aimed to characterize SCA2 patients both clinically and genetically (ATXN2-CAG repeats and its haplotypic background). METHODS: A total of 436 SCA2 patients were recruited consecutively comprising individuals of multiple ethnicities and two large multigenerational families. A detailed clinical evaluation and genetic analysis for CAG repeat length estimation and two marker based haplotype analysis [rs695871 and rs695872 located 177 bp and 106 bp upstream of CAG sequence in Exon 1 of ATXN2] was performed. RESULTS: Generalized limb ataxia and slow saccades were prevalent features in majority of our patients, while hyporeflexia and extrapyramidal features were less commonly observed manifestations. Slow ocular saccades, upper limb ataxia and tremor showed significant associations with age of onset, CAG repeat length and disease duration. We observed a 100% association of C-C haplotype with the expanded ATXN2 repeats. CONCLUSION: This study represents the largest study of SCA2 Indian patients that highlights the clinico-genetic manifestations and haplotype analysis. A significant proportion of patients have not shown the characteristic slow saccades and hyporeflexia thus indicating the influences of other factors in modulation of the disease which warrants further investigations. The observation of CC haplotype in all our SCA2 patients indicates a common origin across all Indian sub populations and that also indicate a common global founder event in the past.

Predictive value of the smell identification test for nigrostriatal dopaminergic depletion in Korean tremor patients.

BACKGROUND: The predictive value of Cross-Cultural Smell Identification Test for nigrostriatal dopaminergic depletion in Korean tremor patients has yet to be assessed. METHODS: Three hundred nineteen drug-naive patients who visited our clinic for the diagnosis of their tremor, and took both Cross-Cultural Smell Identification Test and dopamine transporter PET were included in the data analysis. Visual grading of each PET image was performed by two independent neurologists. RESULTS: Smell test scores were significantly correlated to the striatal dopaminergic activity (Kendall's τb = -0.291, p < 0.001). However, smell test score alone appeared to have relatively weak power for predicting dopaminergic depletion (area under the curve = 0.693). Multivariate logistic regression model with inclusion of the patient's age and symptom duration as independent variables enhanced predictive power for dopaminergic depletion (area under the curve = 0.812). CONCLUSIONS: These results demonstrated that Cross-Cultural Smell Identification Test measurements alone may be insufficient to predict striatal dopaminergic depletion in Korean tremor patients.

Tremor-ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3-10q23.31.

Leukodystrophies are a heterogeneous group of disorders associated with abnormal central nervous system white matter. The clinical features invariably include upper motor neuron signs and developmental regression with or without other neurological manifestations. The objective of this study was to characterize clinically and genetically a new form of childhood-onset leukodystrophy with ataxia and tremor. We recruited seven French-Canadian cases belonging to five families affected by an unknown form of childhood-onset leukodystrophy. Genome-wide scans (GWS) were performed using the Illumina Hap310 or Hap610 Bead Chip to identify regions of shared homozygosity that were further studied for linkage with STS markers. All cases presented between the ages of 1 and 5 years with spasticity along with other upper motor neuron signs, prominent postural tremor, and cerebellar signs. Though motor regression is a constant feature, cognitive functions are relatively preserved, even late in the course of the disease. The higher frequency of founder diseases in the French-Canadian population and the segregation in pedigrees are suggestive of a recessive mode of inheritance. By homozygosity mapping, we established linkage to a 12.6-Mb SNP-haplotyped region on chromosome 10q22.3-10q23.31 (maximum LOD score: 5.47). We describe an autosomal recessive childhood-onset leukodystrophy with ataxia and tremor mapping to a 12.6 Mb interval on chromosome 10q22.3-10q23.31. Identification of the mutated gene will allow precise diagnosis and genetic counseling and shed light on how its perturbed function leads to white matter abnormalities.

Essential tremor might be less frequent than Parkinson's disease in North Israel Arab villages.

Essential tremor (ET) is much more prevalent than Parkinson's disease (PD) in Western countries. We estimated ET and PD prevalence in Wadi Ara Arabic villages in Northern Israel. In this door-to-door survey, all consenting residents aged >or=65 years were systematically examined by an Arabic speaking team. No prescreening questionnaires were used. A random sample of 900 subjects [437 males, mean age (SD) = 72.6 years (6.6)] of the 2,163 eligible residents were evaluated. Sixteen subjects had an action, intentional tremor. Tremor prevalence was estimated as 1.78% (95% CI 1.1-2.87). Nine of these had another likely cause of tremor. Only 7 patients were diagnosed as ET [prevalence 0.78% (95% CI 0.38-1.6)]. PD was diagnosed in 13 subjects. PD prevalence was 1.44% (95% CI 0.84-2.45). ET is unusually uncommon in this population and possibly even less frequent than PD. The PD prevalence in Wadi Ara is similar to that reported in Western countries.

Differences in the prevalence of essential tremor among elderly African Americans, whites, and Hispanics in northern Manhattan, NY.

BACKGROUND: Until now there has been only one community-based study to examine interethnic differences in the prevalence of essential tremor (ET). The study suggested a higher prevalence among whites than African Americans. The present study is the first to examine differences in the prevalence of ET among Hispanics, African Americans, and whites. OBJECTIVE: To estimate the prevalence of essential tremor (ET) in a cohort of community-dwelling elderly of mixed ethnic background. METHODS: A random sample of 2117 Medicare recipients residing in Washington Heights-Inwood in northern Manhattan, NY, were interviewed. A standardized neurological assessment was performed on those who had neurological complaints and on a random sample of those who did not. Essential tremor was defined as a postural or kinetic tremor of the head or limbs. Diagnoses were independently confirmed by two neurologists based on videotaped examination. RESULTS: After age adjustment to the 1990 Washington Heights-Inwood census, the prevalence of ET was 40.2 per 1000 (95% confidence interval, 31.8 to 48.6). Among 46 cases with ET, ET was significantly more prevalent in men than in women (chi 2 = 5.0, P = .03). Prevalence increased significantly with age. The prevalence was higher in whites than African Americans. The prevalence in Hispanics was intermediate. CONCLUSION: The prevalence of ET increases with age and may be higher among men and whites. Prospective studies are needed to further examine these associations.

Prevalence of Parkinson's disease in the Parsi community of Bombay, India.

A door-to-door survey was carried out to screen a community of 14010 people (Parsis living in colonies in Bombay, India) for possible neurologic diseases. High school graduates, social workers, and medical students administered a screening questionnaire that had been shown in a pilot survey to have a sensitivity of 100% for identifying those with Parkinson's disease. Neurologists used defined diagnostic criteria to evaluate individuals positive on the screening survey. There were 46 people (25 men, 21 women) who suffered from Parkinson's disease (328.3 cases per 1000 population). The age-specific prevalence ratios increased consistently with age. Age-adjusted prevalence ratios were slightly higher for men.

Prevalence of essential tremor in the Parsi community of Bombay, India.

A door-to-door survey for neurologic diseases was conducted in a community of 14,010 people (Parsis living in colonies in Bombay, India). Neurologists used defined diagnostic criteria to evaluate persons with positive results on the screening survey. Two hundred thirty-three people (104 men; 129 women) were identified as having essential tremor. The overall prevalence ratio was 1663.1 [corrected] per 100,000 population. Age-specific prevalence ratios increased with age. Age-adjusted prevalence ratios were similar for men and women. To the best of our knowledge, this is the first community-based survey for essential tremor in Asia.